5-Hydroxytryptamine Interaction With The Nicotinic Acetylcholine Receptor
The present study examines the interaction of the neurotransmitter 5- hydroxytryptamine (5-HT) with muscle-type nicotinic acetylcholine receptors. 5-HT inhibits the initial rate of [125I]Î±-bungarotoxin binding to Torpedo acetylcholine receptor membranes (IC50=8.5Â±0.32 mM) and [3H]5-HT can be photoincorporated into acetylcholine receptor subunits, with labeling of the Î±-subunit inhibitable by both agonists and competitive antagonists. Within the agonist-binding domain, [3H]5-HT photoincorporates into Î±Tyr190, Î±Cys192 and Î±Cys193. Functional studies using the human clonal cell line TE671/RD, show that 5-HT is a weak inhibitor (IC50=1.55Â±0.25 mM) of acetylcholine receptor activity. In this regard, agonist-response profiles in the absence and presence of 5-HT indicate a noncompetitive mode of inhibition. In addition, 5-HT displaces high affinity [3H]thienylcyclohexylpiperidine binding to the desensitized Torpedo acetylcholine receptor channel (IC50=1.61Â±0.07 mM). Collectively, these results indicate that 5-HT interacts weakly with the agonist recognition site and inhibits receptor function noncompetitively by binding to the acetylcholine receptor channel. (C) 2000 Elsevier Science B.V.
European Journal of Pharmacology
Digital Object Identifier (DOI)
Blanton, Michael P.; McCardy, Elizabeth A.; Fryer, John D.; Liu, Minghua; and Lukas, Ronald J., "5-Hydroxytryptamine Interaction With The Nicotinic Acetylcholine Receptor" (2000). Neurobiology. 178.